Abstract
Evidence based on thermal stability and enzyme inhibition data suggests that the sulfoxidation of the drug toltrazuril by rat liver microsomes is catalyzed by different cytochromes P-450. Pretreatment of rats by different inducers--phenobarbital, 3-methylcholanthrene, dexamethasone, and triacetyloleandomycin--results in a 2.1-, 2.6-, 2.9-, and 1.8-fold increase, respectively, in the rate of sulfoxidation. The highest increase (8.4-fold) was observed after treatment of microsomes from triacetyloleandomycin-treated animals by potassium ferricyanide. Castration and aging also modify the sulfoxidase activity. The relative rate of formation of the two toltrazuril enantiomers [(A)- and (B)-sulfoxides] depends on the source of the microsomes, suggesting that different cytochromes P-450 have different stereoselectivities.
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